The acquired immunodeficiency syndrome (AIDS) has become a global pandemic, with cases reported in 113 countries throughout the world. An intensive research effort has been undertaken in several countries in the Caribbean, Africa, India, and South America to study the unique epidemiologic, virologic, clinical, and immunologic features of AIDS in these areas. In Kinshasa, Zaire, we have identified over 6,000 cases in 1986 with a male to female ratio of 1:1.3. The disease is predominantly heterosexually transmitted with high seroprevalence rates among spouses of AIDS patients, female prostitutes, and sexually transmitted diseases (STD) clinic populations. The presence of genital ulcerations, history of oral contraceptives and failure to use condoms are all significantly associated with heterosexual transmission. Additional studies within the U.S. have also confirmed the increasing risk of heterosexual transmission. In studies of perinatal transmission of human immunodeficiency virus (HIV), advanced clinical disease and immunologic impairment with depressed T4 cells and reversed T4/T8 ratio are adversely associated with enhanced HIV transmission from mother to infants. In Africa, HIV infection in pregnancy is associated with premature birth, low birth weight, and increased mortality (11%) within the first 3 months of life. Additional serologic and virologic studies have confirmed the presence of a newly identified human retrovirus, referred to as HIV-II, prevalent among patients attending STD clinics. Natural history studies of HIV in Africa have confirmed a 2% annual seroconversion rate among general population and a clinical progression rate similar to that observed in the U.S. Further studies will continue to examine the natural history of HIV infection in patients of developing countries with emphasis on perinatal transmission, safety and efficacy of immunization programs, and genomic changes of viral isolates from diverse regions.